High-performance biosensing based on autonomous enzyme-free DNA circuits

Nucleic acids are considered not only extraordinary carriers of genetic information but also are perceived as the perfect elemental materials of molecular recognition and signal transduction/amplification for assembling programmable artificial reaction networks or circuits, which are similar to conventional electronic logic devices. Among these sophisticated DNA-based reaction networks, catalytic hairpin assembly (CHA), hybridization chain reaction (HCR), and DNAzyme represent the typical nonenzymatic amplification methods with high robustness and efficiency. Furthermore, their extensive hierarchically cascade integration into multi-layered autonomous DNA circuits establishes novel paradigms for constructing more different catalytic DNA nanostructures and for regenerating or replicating diverse molecular components with specific functions. Various DNA and inorganic nanoscaffolds have been used to realize the surface-confined DNA reaction networks with significant biomolecular sensing and signal-regulating functions in living cells. Especially, the specific aptamers and metal-ion-bridged duplex DNA nanostructures could extend their paradigms for detecting small molecules and proteins in even living entities. Herein, the varied enzyme-free DNA circuits are introduced in general with an extensive explanation of their underlying molecular reaction mechanisms. Challenges and outlook of the autonomous enzyme-free DNA circuits will also be discussed at the end of this chapter.